每年近80%的肺癌诊断结果为非小细胞肺癌（NSCLC）。EGFR过表达的NSCLC百分比从40%到89%不等，鳞状肿瘤的比例最高（89%），腺癌的比例最低（41%）。因此，在NSCLC治疗中，通过抑制EGFR的细胞内酪氨酸激酶结构域来阻断EGFR驱动的途径已显示出显著改善。从这个角度来看，数种小分子特别是嘧啶/融合嘧啶骨架旨在进行分子混合，以开发EGFR-TK抑制剂。然而，与药物相关的限制，如耐药性和遗传突变以及不良反应，限制了这类药物的长期治疗和效果。因此，近年来，嘧啶衍生物被发现具有潜在的EGFR TKIs作用。本文综述了EGFR TKIs的研究进展，包括模糊的构效关系、生物评价和嘧啶化合物的对比对接研究。我们进一步添加了对四个不同的EGFR蛋白数据库进行分子对接分析的对比，以加强已有研究。对接分析揭示了化合物14与所有不同的PDB都有明显的相互作用，并且与一些重要的氨基酸残基产生了作用。从未来的角度来看，研究人员必须开发出更有选择性的抑制剂，能够选择性地靶向突变。我们的综述将支持药物化学家朝着开发新型基于嘧啶的EGFR TKIs的方向发展。由Ramaswamy H. Sarma传达。

Almost 80% of lung cancer diagnoses each year correspond to non-small cell lung cancer (NSCLC). The percentage of NSCLC with EGFR overexpression ranges from 40% to 89%, with squamous tumors showing the greatest rates (89%) and adenocarcinomas showing the lowest rates (41%). Therefore, in NSCLC therapy, blocking the EGFR-driven pathway by inhibiting the intracellular tyrosine kinase domain of EGFR has exhibited significant improvement. In this view, several small molecules particularly pyrimidine/fused pyrimidine scaffolds were intended for molecular hybridization to develop EGFR-TK inhibitors. However, the associated limitation such as resistance and genetic mutation along with adverse effects, constrained the long-term treatment and effectiveness of such medication. Therefore, in recent years, pyrimidine derivatives were uncovered as potential EGFR TKIs. The present review summarised the research progress of EGFR TKIs to dazed structure-activity relationship, biological evaluation, and comparative docking studies of pyrimidine compounds. We have added the comparative docking analysis followed by the molecular simulation study against the four different PDBs of EGFR to strengthen the already existing research. Docking analysis unfolded that compound 14 resulted as noticeable with all different PDB and managed to interact with some of the crucial amino acid residues. From a future perspective, researchers must develop a more selective inhibitor, that can selectively target the mutation. Our review will support medicinal chemists in the direction of the development of novel pyrimidine-based EGFR TKIs.Communicated by Ramaswamy H. Sarma.